ArticleProceedings of the National Academy of Sciences of the United States of America2021
Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Importance of the delivery route for the tolerability and efficacy of immunomodulatory agents for lung cancer.Scientific reports · 2026Article
- Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.Science advances · 2026Article
- Design and Characterization of Prodrugged Anti-CTLA-4 Antibodies.Chembiochem : a European journal of chemical biology · 2025Article
- CD137L and colorectal cancer prognosis: Insights from clinical and TCGA data analysis.Cancer biomarkers : section A of Disease markers · 2025Article
- Single-chain Fab chain-exchange (scFab-PACE) converts targeted prodrugs into functional T cell engagers on tumor cells.The Journal of biological chemistry · 2025Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- CD8Nature communications · 2024Article
- Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics.Antibodies (Basel, Switzerland) · 2023Review
- CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects.Science advances · 2023Article
- TCR-independent CD137 (4-1BB) signaling promotes CD8Immunity · 2023Article
- Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.Frontiers in immunology · 2023Review
- Targeting Co-Stimulatory Receptors of the TNF Superfamily for Cancer Immunotherapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- PCSK9 regulates the efficacy of immune checkpoint therapy in lung cancer.Frontiers in immunology · 2023Article
- Targeting CD137 (4-1BB) towards improved safety and efficacy for cancer immunotherapy.Frontiers in immunology · 2023Review
- Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting.Frontiers in immunology · 2023Article
- A Probody T Cell-Engaging Bispecific Antibody Targeting EGFR and CD3 Inhibits Colon Cancer Growth with Limited Toxicity.Cancer research · 2022Article
- Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st-2nd, 2021.Journal of translational medicine · 2022Article
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
- Prodrug-Activating Chain Exchange (PACE) converts targeted prodrug derivatives to functional bi- or multispecific antibodies.Biological chemistry · 2022Article
- Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies.Journal for immunotherapy of cancer · 2022Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Costimulation via CD137 (4-1BB) enhances antitumor immunity mediated by cytotoxic T lymphocytes. Anti-CD137 agonist antibodies elicit mild liver inflammation in mice, and the maximum tolerated dose of Urelumab, an anti-human CD137 agonist monoclonal antibody, in the clinic was defined by liver inflammation-related side effects. A protease-activated prodrug form of the anti-mouse CD137 agonist antibody 1D8 (1D8 Probody therapeutic, Pb-Tx) was constructed and found to be selectively activated in the tumor microenvironment. This construct, which encompasses a protease-cleavable linker holding in place a peptide that masks the antigen binding site, exerted antitumor effects comparable to the unmodified antibody but did not result in liver inflammation. Moreover, it efficaciously synergized with both PD-1 blockade and adoptive T-cell therapy. Surprisingly, minimal active Pb-Tx reached tumor-draining lymph nodes, and regional lymphadenectomy did not abrogate antitumor efficacy. By contrast, S1P receptor-dependent recirculation of T cells was absolutely required for efficacy. The preferential cleavage of the anti-CD137 Pb-Tx by tumor proteases offers multiple therapeutic opportunities, including neoadjuvant therapy, as shown by experiments in which the Pb-Tx is given prior to surgery to avoid spontaneous metastases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.